# Molecular and single-cell immunology of myalgic encephalomyelitis/chronic fatigue syndrome

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $695,556

## Abstract

PROJECT SUMMARY
Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), is a complex, debilitating
disease that has baffled researchers for decades. Its inaccurate yet frequent dismissal as a psychosomatic
condition and lack of recognition by many in the biomedical community have greatly hindered research; as a
result, very little is known about its cause(s), and no biological diagnosis or approved treatments are available.
Recent developments have more clearly defined this mysterious illness, and it is now clear that it afflicts up to
2.5 million in the United States and millions more worldwide. While the symptoms present at various levels,
including neurological and cognitive, widespread molecular and immunological abnormalities have also been
observed. This is consistent with a majority of patients reporting infection prior to the onset of ME/CFS,
although it remains unclear why common infections would serve as triggers for a chronic illness only in some
people. Nevertheless, there is compelling evidence for an active immune response in ME/CFS, as suggested
by elevated levels of signalling molecules called cytokines and activity of killer T cells, which are triggered in
cases of infection or autoimmunity. This proposal aims to uncover the immunological basis of ME/CFS,
by characterizing T cell activity and genetic factors that may be contributing to it using cutting-edge
technologies invented by this team. Firstly, the activity of different T cells will be examined using single-cell
DNA sequencing methods that will determine the extent and nature of their activation, and its regulation by
gene expression. Secondly, the human leukocyte antigen (HLA) locus – the most challenging region of the
human genome to sequence, and the most relevant to individual differences in immunology – will be
sequenced in a large cohort of ME/CFS patients to determine whether HLA variants may be contributing to
the T cell activity observed, and/or to increased susceptibility to the disease. Finally, the molecular triggers of
the immune response will be hunted using cell-free DNA sequencing to detect pathogens, and through
methods to identify which molecules are being targeted by the activated T cells. Taken together, these
findings will help to identify the molecular and immunological factors that trigger and/or sustain ME/CFS as a
chronic illness, and whether its basis is infectious, autoimmune, or both. More broadly, this project will build a
precise framework for ME/CFS as a molecular and immunological disease, opening up broad new
possibilities for research, diagnosis, and treatment. Understanding the molecular nature of the immune
response in ME/CFS may lead to the definition of clinically valuable subtypes, refined diagnostics, risk
prediction, and personalized immunomodulatory therapies. Moreover, the similarity of ME/CFS to other
medically challenging diseases like Lyme disease, multiple sclerosis, Gulf War Illness, fibromyalgia, and more...

## Key facts

- **NIH application ID:** 10416027
- **Project number:** 5R01AI139550-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ronald Wayne Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $695,556
- **Award type:** 5
- **Project period:** 2018-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416027

## Citation

> US National Institutes of Health, RePORTER application 10416027, Molecular and single-cell immunology of myalgic encephalomyelitis/chronic fatigue syndrome (5R01AI139550-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10416027. Licensed CC0.

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